The major obstacle to improving the outcome of autologous transplantation for hematologic malignancy is post-transplant relapse. Accordingly, the studies proposed in Project will focus on the following: i) Decreasing post-transplant relapse by studying intensive multi-modality preparative regimens followed by IL-2 cytokine therapy, ii) Decreasing post-transplant relapse by studying intensive multi-modality preparative regimens for lymphoma, AML and myelodysplasia, iii) Targeting post- transplant minimal residual disease by the adoptive transfer of tumor- specific T-cells, and iv) Genetically modifying autologous hematopoietic stem cells to resist HIV infection in the setting of autologous transplantation for HIV lymphoma. Specifically, transplant regimens piloted at City of Hope for the treatment of AML that incorporate post- transplant high-dose IL-2 will be expanded to validate the promising survival data seen in pilot studies. Yttrium labeled anti-CD33 antibody and anti-CD20 antibody will be incorporated into the preparative regimens for patients with poor prognosis myeloid malignancy and B-cell lymphoma, respectively. Cellular immunotherapy with autologous CTL clones genetically-modified to express a CD20-specific chimeric immuno receptor infused shortly following stem cell transplantation for recurrent diffuse large cell lymphoma will be piloted. Hematopoietic stem cells modified with adeno-associated virus and lenti virus vectors containing anti-retroviral transgenes will be evaluated as a strategy to reconstitute HIV-resistant cellular immunity in HIV patients undergoing stem cell transplantation for lymphoma during the era of HAART therapy. Project II will serve as a clinical resource for the experimental Projects IV, V and VI.